Albuminuria is directly associated with increased plasma PAI-1 and factor VII levels in NIDDM patients

Abstract

Increased plasma plasminogen activator inhibitor type 1 (PAI-1), coagulation factor VII (FVII) and fibrinogen levels have been recognized as risk factors for cardiovascular disease. Because a substantially high incidence of cardiovascular disease has been reported in diabetic patients with nephropathy compared with those without nephropathy, we measured plasma levels of PAI-1, FVII activity and fibrinogen in non-insulin-dependent diabetic patients (NIDDM) with normoalbuminuria (without nephropathy), microalbuminuria (incipient nephropathy) and macroalbuminuria (overt nephropathy). PAI-1 and FVII levels were significantly increased in NIDDM with overt nephropathy compared with NIDDM without nephropathy. Fibrinogen levels were comparable between the patients with normo-, micro- and macro-albuminuria. Univariate regression analysis indicated that PAI-1 and FVII levels were significantly correlated with the albumin excretion rate (AER) in urine. PAI-1, FVII and fibrinogen levels were significantly correlated with the degree of insulin resistance estimated by the steady state plasma glucose concentration (SSPG) during the continuous infusion of glucose, insulin and octreotide. PAI-1 levels were correlated with plasma triglyceride (TG) levels. Multiple regression analysis revealed that AER was significantly associated with PAI-1 and FVII levels, whereas TG lost significant correlation with PAI-1 when AER, SSPG and plasma TG were entered as independent variables. SSPG retained an independent correlation with fibrinogen, PAI-1 and FVII levels. These results suggest that elevated plasma levels of PAI-1 and FVII in NIDDM patients with nephropathy are directly associated with renal damage, whereas insulin resistance widely regulates hemostatic components in NIDDM patients, irrespective of the presence of nephropathy.